The Translational Core of this Hepatitis C (HCV) Cooperative Research Center is focused on three aims: (i) to describe the clinical consequences of long-standing HCV disease;(ii) to identify rates and predictors of fibrosis progression measured in patients undergoing two liver biopsies and;(iii) to serve as a resource for studies and HCV resolution, persistence and pathogenesis. The rationale for these aims is as follows: The natural history of HCV infection is poorly defined. While we currently have therapies that eradicate HCV, it is unclear whether treatment modifies the natural history of disease and/or whether treatment should be initiated in patients with mild liver disease. This decision is problematic since many patients with HCV are 50 years old, and are potentially at risk for developing life determining non-hepatic conditions that may reduce life expectancy independent of HCV infection. This study will test the hypothesis that non-hepatic clinical events will occur more frequently than liver complications in patients with mild liver disease and conversely that hepatic complications will be more common than non-hepatic clinical events in patients with advanced disease. To test this hypothesis we have the following specific aims: Specific aim #1 To measure current hepatic and non-hepatic clinical status in more than 775 well-characterized HCV monoinfected patients who have undergone liver biopsy at SFVAMC/UCSF in the past ten years. Patients will be dichotomized into those with early disease (fibrosis stage 0,1,2) and those with advanced disease (fibrosis stage 3 or 4). Liver disease-related clinical endpoints will be defined as development of an increase in two points or more in Child-Pugh score, esophageal variceal bleeding, spontaneous bacterial peritonitis, hepatocellular carcinoma or death from liver disease. Non-hepatic clinical end-points will be defined as development of symptomatic coronary artery disease, non-hepatic malignancy (other than skin cancer), other life-threatening medical conditions such as severe chronic obstructive pulmonary disease, or non-liver-related death. Predictors of these hepatic and non-hepatic outcomes, obtained at the time of initial liver biopsy (baseline) and in this study period will be measured. Specific aim #2 To determine histological disease progression measured by change in fibrosis score in our cohort between prior liver biopsies and additional biopsies performed in the proposed study period. This aim includes the collection of data that could influence progression such as demographics, lifestyle (alcohol use, BMI, injection drug use), markers of liver injury (serum alanine aminotransferase, albumin, bilirubin, prothrombin time), viral factors (HCV RNA level, genotype), HCV antiviral therapy (response and non-response), age at onset and duration of infection, the presence or absence of a miss-sense mutation in the DEAD box gene as well as the severity of initial liver histology measured by fibrosis stage, inflammation and steatosis. Specific aim #3 To serve as a resource for our collaborators by providing clinical data and specimens from cohorts of patients with acute and chronic HCV.